Network-based bioinformatics highlights broad importance of human milk hyaluronan
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1145472 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30164517_1.fastq.gz | Fastqsanger.gz | |||
| SRR30164517_2.fastq.gz | Fastqsanger.gz | |||
| SRR30164518_1.fastq.gz | Fastqsanger.gz | |||
| SRR30164518_2.fastq.gz | Fastqsanger.gz | |||
| SRR30164519_1.fastq.gz | Fastqsanger.gz |
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Project description:Hyaluronic acid 35 kDa (HA35) is protective against murine necrotizing enterocolitis and is present in high levels in colostrum and early human milk. We utilized pathway and network analysis of bulk RNA-seq transcriptomics of the distal ileum of mouse pups to determine molecular mechanisms through which HA35 may influence small intestinal maturation and protection against inflammatory disease.
2024-12-19 | GSE274261 | GEO
Project description:Human milk (HM) is rich in bioactive factors promoting postnatal small intestinal development and maturation of the microbiome. HM is also protective against necrotizing enterocolitis (NEC), a devastating inflammatory condition predominantly affecting preterm infants. The HM glycosaminoglycan, hyaluronan (HA), is present at high levels in colostrum and early milk. Our group has demonstrated that HA with a molecular weight of 35 kDa (HA35) promotes maturation of the murine neonatal intestine and protects against two distinct models of NEC. However, the molecular mechanisms underpinning HA35-induced changes in the developing ileum are unclear. CD-1 mouse pups were treated with HA35 or vehicle control daily, from P7 to P14, and we used network and functional analyses of bulk RNA-seq ileal transcriptomes to further characterize molecular mechanisms through which HA35 likely influences intestinal maturation. HA35-treated pups separated well by principal component analysis, and cell deconvolution revealed increases in stromal, Paneth, and mature enterocyte and progenitor cells in HA35-treated pups. Gene set enrichment and pathway analyses demonstrated upregulation in key processes related to antioxidant and growth pathways, such as nuclear factor erythroid 2-related factor-mediated oxidative stress response, hypoxia inducible factor-1 alpha, mechanistic target of rapamycin, and downregulation of apoptotic signaling. Collectively, pro-growth and differentiation signals induced by HA35 may present novel mechanisms by which this HM bioactive factor may protect against NEC.
| S-EPMC11641400 | biostudies-literature
Project description:Investigation of the role of hyaluronan in cardiomyocytes . The aims of the study were to determine if cardiomyocytes are capable of detecting hyaluronan and if then intrecellular signaling causes changes in gene expression. The study showed that cardiomyocytes can bind hyaluronan with following change in gene expression.
2011-11-01 | GSE21675 | GEO
Project description:Background: The extracellular matrix provides organizational context for solid organs. During disease, such as acute myocardial infarction, the composition of the extracellular matrix changes remarkably. One of the most notable changes in the extracellular matrix is in the accumulation of collagen; however, hyaluronan rivals collagen in terms of its abundance. Yet, the extent to which specific cells and enzymes may contribute to such accumulation has been largely unexplored. Here, we hypothesized that activated cardiac fibroblasts produce hyaluronan via hyaluronan synthase 2 (HAS2). Methods and Results: Using immunofluorescence, biochemical extraction, and ELISA, we show that hyaluronan accumulates following myocardial infarction and persists through at least four weeks. Our analyses of failing heart RNA sequencing data suggest fibroblasts are the cells most changed in expression of HAS2. Given these insights, we used HAS2 gain- and loss-of-function approaches to examine the extent to which activated cardiac fibroblasts produced hyaluronan. TGF-induced activation of fibroblasts caused a significant increase in Has2 mRNA and concomitant accumulation of hyaluronan greater than 1 MDa in size. Deletion of Has2 abrogated TGF-induced production of hyaluronan. In addition, overexpression of Has2 was sufficient to cause an increase in hyaluronan accumulation in the absence of TGF-induced activation. Given the magnitude of hyaluronan production, and that hyaluronan has been reported to have biologic activity, we then queried whether the primary functions of fibroblasts (proliferation, migration, and collagen production) were impacted by hyaluronan treatment. Our data indicated negligible impacts of Has2 on proliferation, migration, and collagen production. Exposing fibroblasts to exogenous hyaluronan also had minimal impact on fibroblasts. We also assessed whether fibroblast-borne Hyal2 plays a role in degradation of hyaluronan, and our data indicated little impact of Hyal2 on hyaluronan accumulation (or even any impacts on the transcriptional profile of fibroblasts). Conclusion: Activated fibroblasts produce high molecular weight hyaluronan, and the production of hyaluronan depends on Has2. The robust production of hyaluronan by fibroblasts does not appear to impact fibroblast function.
2026-01-30 | GSE284092 | GEO
Project description:Background: The extracellular matrix provides organizational context for solid organs. During disease, such as acute myocardial infarction, the composition of the extracellular matrix changes remarkably. One of the most notable changes in the extracellular matrix is in the accumulation of collagen; however, hyaluronan rivals collagen in terms of its abundance. Yet, the extent to which specific cells and enzymes may contribute to such accumulation has been largely unexplored. Here, we hypothesized that activated cardiac fibroblasts produce hyaluronan via hyaluronan synthase 2 (HAS2). Methods and Results: Using immunofluorescence, biochemical extraction, and ELISA, we show that hyaluronan accumulates following myocardial infarction and persists through at least four weeks. Our analyses of failing heart RNA sequencing data suggest fibroblasts are the cells most changed in expression of HAS2. Given these insights, we used HAS2 gain- and loss-of-function approaches to examine the extent to which activated cardiac fibroblasts produced hyaluronan. TGF-induced activation of fibroblasts caused a significant increase in Has2 mRNA and concomitant accumulation of hyaluronan greater than 1 MDa in size. Deletion of Has2 abrogated TGF-induced production of hyaluronan. In addition, overexpression of Has2 was sufficient to cause an increase in hyaluronan accumulation in the absence of TGF-induced activation. Given the magnitude of hyaluronan production, and that hyaluronan has been reported to have biologic activity, we then queried whether the primary functions of fibroblasts (proliferation, migration, and collagen production) were impacted by hyaluronan treatment. Our data indicated negligible impacts of Has2 on proliferation, migration, and collagen production. Exposing fibroblasts to exogenous hyaluronan also had minimal impact on fibroblasts. We also assessed whether fibroblast-borne Hyal2 plays a role in degradation of hyaluronan, and our data indicated little impact of Hyal2 on hyaluronan accumulation (or even any impacts on the transcriptional profile of fibroblasts). Conclusion: Activated fibroblasts produce high molecular weight hyaluronan, and the production of hyaluronan depends on Has2. The robust production of hyaluronan by fibroblasts does not appear to impact fibroblast function.
2026-01-30 | GSE284546 | GEO
Project description:Background: The extracellular matrix provides organizational context for solid organs. During disease, such as acute myocardial infarction, the composition of the extracellular matrix changes remarkably. One of the most notable changes in the extracellular matrix is in the accumulation of collagen; however, hyaluronan rivals collagen in terms of its abundance. Yet, the extent to which specific cells and enzymes may contribute to such accumulation has been largely unexplored. Here, we hypothesized that activated cardiac fibroblasts produce hyaluronan via hyaluronan synthase 2 (HAS2). Methods and Results: Using immunofluorescence, biochemical extraction, and ELISA, we show that hyaluronan accumulates following myocardial infarction and persists through at least four weeks. Our analyses of failing heart RNA sequencing data suggest fibroblasts are the cells most changed in expression of HAS2. Given these insights, we used HAS2 gain- and loss-of-function approaches to examine the extent to which activated cardiac fibroblasts produced hyaluronan. TGF-induced activation of fibroblasts caused a significant increase in Has2 mRNA and concomitant accumulation of hyaluronan greater than 1 MDa in size. Deletion of Has2 abrogated TGF-induced production of hyaluronan. In addition, overexpression of Has2 was sufficient to cause an increase in hyaluronan accumulation in the absence of TGF-induced activation. Given the magnitude of hyaluronan production, and that hyaluronan has been reported to have biologic activity, we then queried whether the primary functions of fibroblasts (proliferation, migration, and collagen production) were impacted by hyaluronan treatment. Our data indicated negligible impacts of Has2 on proliferation, migration, and collagen production. Exposing fibroblasts to exogenous hyaluronan also had minimal impact on fibroblasts. We also assessed whether fibroblast-borne Hyal2 plays a role in degradation of hyaluronan, and our data indicated little impact of Hyal2 on hyaluronan accumulation (or even any impacts on the transcriptional profile of fibroblasts). Conclusion: Activated fibroblasts produce high molecular weight hyaluronan, and the production of hyaluronan depends on Has2. The robust production of hyaluronan by fibroblasts does not appear to impact fibroblast function.
2026-01-30 | GSE284157 | GEO
Project description:Dysregulated redox signaling contributes to pulmonary hypertension (PH) and vascular-selective depletion of the redox enzyme EC-SOD (EC-SOD SMC KO) worsens chronic hypoxic PH. Given the important role of macrophages in vascular remodeling and PH, this study aimed to determine if interstitial macrophages (IMs) and their interactions with the extracellular matrix (ECM) component, hyaluronan, are modulated by vascular EC-SOD. Floxed wild-type (WT), EC-SOD SMC KO, and EC-SOD mimetic- or vehicle-treated mice were exposed to hypobaric hypoxia (~10% FiO2), for 4, 14, or 21 days. Using flow cytometry, we demonstrated that the transient increase in IMs at day 4 was exacerbated in EC-SOD SMC KO mice and prevented with EC-SOD mimetic (5 mg/kg, subcutaneous, day 1). Highlighting the importance of targeting vascular oxidative stress in the early response to hypoxia, pretreatment with this single dose of EC-SOD mimetic decreased right ventricular systolic pressure, right ventricular hypertrophy, and small vessel muscularization at day 21. To assess IM phenotypic reprogramming in this model, RNAseq was performed on flow-sorted IMs revealing baseline proinflammatory activation and enhanced activation of vascular and ECM remodeling pathways in response to hypoxia in EC-SOD SMC KO IMs compared to controls. To further investigate the ECM remodeling response, we quantified IMs expressing the hyaluronan receptor Lyve1, and IM-hyaluronan binding. Lyve1+IMs and Lyve1+HA+IMs were increased in response to hypoxia in EC-SOD SMC KO mice and accumulated in the perivascular space. In conclusion, vascular EC-SOD limits IM accumulation and proinflammatory profibrotic IM signaling, including perivascular accumulation of Lyve1+IMs and their binding to hyaluronan.
2025-09-24 | GSE283567 | GEO
Project description:This project investigates proteomic adaptations of Bacteroides thetaiotaomicron and Bacteroides acidifaciens in response to hyaluronan as the sole glycosaminoglycan carbon source. Both species were cultivated in a standard medium and in a hyaluronan-based minimal medium, and their proteomes were analyzed by LC-MS/MS. The study aimed to identify global shifts in protein expression between growth conditions and to pinpoint specific proteins involved in hyaluronan degradation pathways. Comparative analysis between the two cultivation conditions provides insight into how gut-associated Bacteroides species regulate metabolic and enzymatic machinery for glycosaminoglycan utilization.
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Project description:We identified the changes in gene expression profile in hyaluronan-induced spheroids to elucidate the mechanisms of drug resistance of extramedullary disease in multiple myeloma.
2022-07-31 | GSE189364 | GEO
Project description:Tissue resident macrophages in the mammary gland are found in close association with epithelial structures and within the adipose stroma, and are important for mammary gland development and tissue homeostasis. While epithelial-associated macrophages have been linked to ductal development, the contributions of stromal macrophages to mammary gland homeostasis remain unknown. Using transcriptional profiling, we identify a distinct resident stromal macrophage subpopulation that is characterized by expression of Lyve-1, a receptor for the extracellular matrix component hyaluronan. This subpopulation is enriched in genes associated with extracellular matrix remodeling and is found to be specifically associated with hyaluronan-rich regions within the mammary stroma. Furthermore, macrophage depletion leads to increased accumulation of hyaluronan-associated extracellular matrix in the mammary stroma. These results demonstrate the presence of a distinct subpopulation of macrophages and provide insights into the functional contributions of these macrophages to stromal homeostasis in the mammary gland.
2020-05-31 | GSE148207 | GEO